Hormonal influences on hemostasis in women

Hemostasis in women is influenced by physiological changes in hormone status associated with the menstrual cycle, pregnancy and hormone-based contraceptives, and hormone replacement therapy (HRT) preparations. These hormonal influences can lead to an increase in the risk of venous thromboembolism (VTE) due to altered levels of clotting factors and an acquired resistance to the actions of activated protein C. This articles reviews recent evidence for these changes. During the menstrual cycle, changes are observed in levels of von Willebrand factor (VWF), fibrinogen, and activated factor VII. No such effect has been demonstrated in protein S or protein C levels or activated protein C resistance. Pregnancy is a procoagulant state with progressive increase in levels of factors VII, VIII, X, and XII, fibrinogen, and VWF, as well as increased resistance to activated protein C. Hormonal contraceptives and HRT are widely used and have undergone many changes over the years. Recent modifications to the preparations used in combined oral contraceptives (COC) aimed at improving side-effect profiles have also been shown to increase the risk of VTE for third- and fourth-generation COC compared with second-generation COC. This has been shown to be due to changes in activated protein C resistance. This risk of VTE represents a significant public health issue, but increased awareness and further research may allow development of safer future therapies leading to improvements in women's health.